In solid tumors, glycolytic cancer or stromal cells export lactates through monocarboxylate transporter (MCT) 4, while oxidative cancer or stromal cells take up lactates as metabolic fuels or signaling molecules through MCT1. CD147 acts as a chaperone of MCT1 or MCT4. Unlike solid tumors, malignant lymphomas have a peculiar tumor microenvironment. To investigate the metabolic phenotype of malignant lymphoma associated with lactate transport, we analyzed immunohistochemical expressions of MCT1, MCT4, and CD147 in 247 cases of various malignant lymphomas. Surprisingly, both MCT1 and MCT4 were diffusely expressed on tumor cell membranes in all cases (11/11, 100%) of anaplastic lymphoma kinase (ALK) (+) anaplastic large cell lymphoma (ALCL). In contrast, only MCT1 was diffusely expressed in tumor cells of ALK(−) ALCL, as well as in B-cell, natural killer/T-cell, T-cell, and classic Hodgkin lymphomas. In these lymphomas, MCT4 expression was mostly localized to adjacent stromal cells. The pattern of diffuse membranous MCT1 and partial MCT4 expressions in tumor cells was observed in 1 case each of peripheral T-cell lymphoma (1/15, 6.7%) and multiple myeloma (1/34, 2.9%). CD147 was diffusely expressed in all types of lymphoma tumor and/or stromal cells. In conclusion, ALK(+) ALCL has a unique metabolism showing high coexpression of MCT1 and MCT4 in tumor cells. Because only ALK(+) ALCL overexpresses MCT4, immunostaining for MCT4 together with ALK is very useful for differential diagnosis from ALK(−) ALCL or peripheral T-cell lymphoma. Moreover, dual targeting against MCT1 and MCT4 would be an appropriate therapeutic approach for ALK(+) ALCL.

在实体瘤中，糖酵解癌或基质细胞通过单羧酸转运蛋白(MCT) 4 输出乳酸，而氧化癌或基质细胞通过 MCT1 吸收乳酸作为代谢燃料或信号分子。CD147 充当 MCT1 或 MCT4 的伴侣。与实体瘤不同，恶性淋巴瘤具有独特的肿瘤微环境。为了研究与乳酸转运相关的恶性淋巴瘤的代谢表型，我们分析了 247 例各种恶性淋巴瘤中 MCT1、MCT4 和 CD147 的免疫组织化学表达。令人惊讶的是，在所有间变性淋巴瘤激酶（ALK）（+）间变性大细胞淋巴瘤（ALCL）病例（11/11，100%）中，MCT1和MCT4均在肿瘤细胞膜上广泛表达。相比之下，只有 MCT1 在 ALK(−) ALCL 的肿瘤细胞以及 B 细胞、自然杀伤/T 细胞、T 细胞和经典霍奇金淋巴瘤中广泛表达。在这些淋巴瘤中，MCT4 表达主要局限于邻近的基质细胞。外周T细胞淋巴瘤（1/15，6.7%）和多发性骨髓瘤（1/34，2.9%）各1例中观察到肿瘤细胞弥漫膜性MCT1和部分MCT4表达模式。CD147在所有类型的淋巴瘤肿瘤和/或基质细胞中广泛表达。总之，ALK(+) ALCL 具有独特的代谢，显示肿瘤细胞中 MCT1 和 MCT4 的高度共表达。由于只有 ALK(+) ALCL 过表达 MCT4，因此 MCT4 与 ALK 一起进行免疫染色对于与 ALK(−) ALCL 或外周 T 细胞淋巴瘤的鉴别诊断非常有用。此外，针对 MCT1 和 MCT4 的双重靶向将是 ALK(+) ALCL 的合适治疗方法。